产前诊断羊水细胞Y染色体异常七例分析

doi:10.12280/gjfckx.20250032

摘要/Abstract

摘要：

目的：分析7例产前检测羊水细胞提示Y染色体异常的病例，总结不同检测方法结果之间的联系，合理判读结果以指导产前遗传咨询。方法：收集产前检测提示Y染色体异常的7例病例资料，产前检测方式包括羊水细胞染色体核型分析、染色体微阵列分析、多重连接探针扩增技术、荧光原位杂交技术和光学基因组图谱分析技术，根据各检测方法的特点和检测结果综合判断得出最接近真实的染色体结果。结果：7例Y染色体异常病例中，有6例为嵌合体（病例2除外）。病例1、2、6、7的各检测方法所提示Y染色体异常的情况基本一致，而病例3、4、5的各检测方法出现了不同的结果。结论：在胎儿染色体的检查中，为了避免Y染色体结果的评估出现偏颇，建议进行以染色体核型分析为基础，叠加其他各种分子和细胞遗传学检测的方式，使Y染色体的信息能得到更全面的体现。临床医生需根据Y染色体异常的类型和各检测方法的结果，综合评估胎儿出生后可能出现的临床表现，从而做出正确的临床指导。

关键词: 产前诊断, Y染色体, 性染色体畸变, 核型分析, 微阵列分析, 遗传咨询

Abstract:

Objective: To analyze 7 cases of Y chromosome abnormalities detected in amniotic fluid cells through prenatal testing, evaluate the correlations between different testing methodologies, and provide guidance for accurate interpretation of results in prenatal genetic counseling. Methods: We retrospectively reviewed 7 cases with prenatal testing diagnosis of Y chromosome abnormalities. Testing modalities included karyotype analysis, chromosomal microarray analysis (CMA), multiplex ligation-dependent probe amplification (MLPA), fluorescence in situ hybridization (FISH), and optical genome mapping(OGM). Comprehensive results were derived by integrating findings from these complementary techniques. Results: Among the 7 cases, 6 exhibited mosaics (excluding Case 2). Case 1, 2, 6, and 7 showed consistent Y chromosome abnormalities across all testing methods. In contrast, Case 3, 4, and 5 demonstrated discordant results between techniques. Conclusions: For accurate assessment of fetal Y chromosome status, we recommended a combined approach utilizing conventional karyotyping supplemented by molecular and cytogenetic methods(CMA/MLPA/FISH/OGM) to obtain comprehensive genomic information. Clinicians should correlate the specific type of Y chromosome abnormality with test results to predict potential postnatal phenotypes and provide appropriate genetic counseling.

Key words: Prenatal diagnosis, Y chromosome, Sex chromosome aberrations, Karyotyping, Microarray analysis, Genetic counseling

周静, 季修庆, 李璃, 刘安, 王玉国, 周冉, 许争峰. 产前诊断羊水细胞Y染色体异常七例分析[J]. 国际妇产科学杂志, 2025, 52(4): 394-401.

ZHOU Jing, JI Xiu-qing, LI Li, LIU An, WANG Yu-guo, ZHOU Ran, XU Zheng-feng. Prenatal Diagnosis of Y Chromosome Abnormalities in Amniotic Fluid Cells: A Case Series of 7 Cases[J]. Journal of International Obstetrics and Gynecology, 2025, 52(4): 394-401.

图/表 7

图1 病例1产前诊断结果注：A 羊水细胞染色体核型分析提示只有1条X染色体且15号和22号染色体罗伯逊易位；B 羊水染色体核型分析提示2条Y染色体长臂末端q11.222q11.23区段缺失后重新连接形成双着丝粒染色体，且15号和22号染色体罗伯逊易位；C CMA结果提示Y染色体缺失区段含有AZFb和AZFc区；D CMA结果提示Y染色体q11.222q11.23区段部分缺失；E CMA结果提示17号染色体p12p11.2区段部分重复

图2 病例2产前诊断结果注：A CMA结果提示Y染色体部分重复和部分缺失，且缺失区段含有AZFb和AZFc区；B CMA结果提示Y染色体q11.221q11.23区段部分缺失

图3 病例3产前诊断结果注：A 羊水细胞染色体核型分析提示只有1条X染色体；B 羊水细胞染色体核型分析提示2条Y染色体长臂末端q12区段缺失后重新连接形成双着丝粒染色体；C MLPA结果提示Y染色体含量增加

图4 病例4产前诊断结果注：A 羊水细胞染色体核型分析提示只有1条X染色体；B 羊水细胞染色体核型分析提示Y染色体长臂末端缺失；C CMA结果提示2号染色体p12区段部分重复；D CMA结果提示Y染色体q11.223q11.23区段部分缺失

图5 病例5产前诊断结果注：A 羊水细胞染色体核型分析提示只有1条X染色体；B 羊水细胞染色体核型分析提示2条Y染色体短臂末端p11.32区段缺失后重新连接形成双着丝粒染色体；C FISH结果显示此细胞1个X探针信号，提示仅有1条X染色体；D FISH结果显示此细胞1个X探针信号和2个Y探针信号，提示有1条X染色体和2条Y染色体

图6 病例6产前诊断结果注：A 羊水细胞染色体核型分析提示只有1条X染色体且15号染色体出现随体柄长度增加；B 羊水细胞染色体核型分析提示2条Y染色体长臂末端q11.221q11.23区段缺失后重新连接形成双着丝粒染色体，15号染色体出现随体柄长度增加；C CMA结果提示Y染色体缺失区段含有AZFb和AZFc区；D CMA结果提示Y染色体q11.221q11.23区段部分缺失；E OGM环形图显示X染色体缺失；F OGM结果显示参考基因组图谱和样本基因组图谱对比后转折点在Yq11.221，形成双着丝粒的Y染色体

图7 病例7产前诊断结果注：A 羊水细胞染色体核型分析提示只有1条X染色体；B 羊水细胞染色体核型分析提示2条Y染色体长臂末端q11.222q11.23区段缺失后重新连接形成双着丝粒染色体；C CMA结果提示Y染色体缺失区段含有AZFb和AZFc区；D CMA结果提示Y染色体q11.222q11.23区段部分缺失

参考文献 21

[1]	Yin H, Xie H, Zou J, et al. A mosaic karyotype of 45,X/46,X,psu idic(Y)(q12) in a ten-year-old boy: integrating high-throughput sequencing with cytogenetic technique for precise diagnosis and genetic counselling[J]. BMC Pediatr, 2023, 23(1):104. doi: 10.1186/s12887-023-03872-y. pmid: 36870983
[2]	Zhang Q, Chen X, Cao Y, et al. 45,X[2]/46,X,der(Y).ish Psu idic(Y)(q11.2)[38] mosaic karyotype in mixed gonadal dysgenesis: a case report and literature review[J]. Front Pediatr, 2024, 12:1460174. doi: 10.3389/fped.2024.1460174.
[3]	Colaco S, Modi D. Consequences of Y chromosome microdeletions beyond male infertility[J]. J Assist Reprod Genet, 2019, 36(7):1329-1337. doi: 10.1007/s10815-019-01492-z.
[4]	Vogt PH. Human chromosome deletions in Yq11, AZF candidate genes and male infertility: history and update[J]. Mol Hum Reprod, 1998, 4(8):739-744. doi: 10.1093/molehr/4.8.739. pmid: 9733430
[5]	Dirican CD, Nelson PS. Y Chromosome Loss and Implications for Oncology[J]. Mol Cancer Res, 2024, 22(7):603-612. doi: 10.1158/1541-7786.MCR-24-0105.
[6]	Weyrich M, Cremer S, Gerster M, et al. Loss of Y Chromosome and Cardiovascular Events in Chronic Kidney Disease[J]. Circulation, 2024, 150(10):746-757. doi: 10.1161/CIRCULATIONAHA.124.069139.
[7]	Kalantari H, Asia S, Totonchi M, et al. Delineating the association between isodicentric chromosome Y and infertility: a retrospective study[J]. Fertil Steril, 2014, 101(4):1091-1096. doi: 10.1016/j.fertnstert.2013.12.048. pmid: 24502892
[8]	Shetty RA, Shetty DP, Kulshreshtha PS, et al. Mixed Gonadal Dysgenesis with 45,X/46,X,idic(Y)/46,XY Karyotype: A Case Report[J]. J Reprod Infertil, 2024, 25(1):72-76. doi: 10.18502/jri.v25i1.15203. pmid: 39157281
[9]	He Y, Guo L, Zheng L, et al. Clinical and molecular cytogenetic findings and pregnancy outcomes of fetuses with isochromosome Y[J]. Mol Cytogenet, 2022, 15(1):32. doi: 10.1186/s13039-022-00611-3. pmid: 35927742
[10]	Tuck-Muller CM, Chen H, Martínez JE, et al. Isodicentric Y chromosome: cytogenetic, molecular and clinical studies and review of the literature[J]. Hum Genet, 1995, 96(1):119-129. doi: 10.1007/BF00214200. pmid: 7607645
[11]	Si YM, Dong Y, Wang W, et al. Hypospadias in a male infant with an unusual mosaic 45,X/46,X,psu idic(Y)(p11.32)/46,XY and haploinsufficiency of SHOX: A case report[J]. Mol Med Rep, 2017, 16(1):201-207. doi: 10.3892/mmr.2017.6569.
[12]	DesGroseilliers M, Beaulieu Bergeron M, Brochu P, et al. Phenotypic variability in isodicentric Y patients: study of nine cases[J]. Clin Genet, 2006, 70(2):145-150. doi: 10.1111/j.1399-0004.2006.00654.x. pmid: 16879197
[13]	Lange J, Skaletsky H, van Daalen SK, et al. Isodicentric Y chromosomes and sex disorders as byproducts of homologous recombination that maintains palindromes[J]. Cell, 2009, 138(5):855-869. doi: 10.1016/j.cell.2009.07.042. pmid: 19737515
[14]	Cong X, Zhang T, Li Z, et al. Prenatal diagnosis of a trisomy 7 mosaic case: CMA, CNV-seq, karyotyping, interphase FISH, and MS-MLPA, which technique to choose?[J]. BMC Pregnancy Childbirth, 2024, 24(1):338. doi: 10.1186/s12884-024-06522-y.
[15]	Kim JW, Park SY, Ryu HM, et al. Molecular and clinical characteristics of 26 cases with structural Y chromosome aberrations[J]. Cytogenet Genome Res, 2012, 136(4):270-277. doi: 10.1159/000338413. pmid: 22688216
[16]	宋明哲, 孙莹璞, 孙海翔, 等. 无精子症不育诊断和治疗中国专家共识[J]. 生殖医学杂志, 2023, 32(1):9-18. doi: 10.3969/j.issn.1004-3845.2023.01.002.
[17]	Abur U, Gunes S, Hekim N, et al. Clinical, cytogenomic, and molecular characterization of isodicentric Y-chromosome and prediction of testicular sperm retrieval outcomes in azoospermic and severe oligozoospermic infertile men[J]. J Assist Reprod Genet, 2022, 39(12):2799-2810. doi: 10.1007/s10815-022-02632-8.
[18]	Han Y, Wu J, Tan F, et al. 45,X/46,X,psu idic(Y)(q11.2) Mosaicism in a Primary Amenorrhea Girl with Swyer Syndrome[J]. Case Rep Genet, 2023, 2023:9127512. doi: 10.1155/2023/9127512.
[19]	Xu Y, Zhang Q, Wang Y, et al. Optical Genome Mapping for Chromosomal Aberrations Detection-False-Negative Results and Contributing Factors[J]. Diagnostics(Basel), 2024, 14(2):165. doi: 10.3390/diagnostics14020165.
[20]	Krausz C, Casamonti E. Spermatogenic failure and the Y chromosome[J]. Hum Genet, 2017, 136(5):637-655. doi: 10.1007/s00439-017-1793-8. pmid: 28456834
[21]	Krausz C, Navarro-Costa P, Wilke M, et al. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: State of the art 2023[J]. Andrology, 2024, 12(3):487-504. doi: 10.1111/andr.13514.